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Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results., Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10., Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview., Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88)., Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression., (© 2019 S. Karger AG, Basel.)

Background: Although growing evidence indicates that ECT affects astrocytes, the exact mechanisms of the therapeutic effect of ECT are still unknown. Astrocytic endfeet express the water channel aquaporin (AQP) 4 abundantly and ensheath brain blood vessels to form gliovascular units. It has been shown that the coverage of blood vessels by AQP4-immunostained endfeet is decreased in the prefrontal cortex (PFC) of patients with major depression. This study was made to determine whether ECT restores the astrocytic coverage of blood vessels with amelioration of depressive symptoms., Methods: After electroconvulsive shock (ECS) administration to rats, the forced swimming test (FST) and Y-maze test were performed. Subsequently, immunofluorescence analysis was conducted to measure the coverage of blood vessels by astrocytic endfeet in the PFC and hippocampus by using the endothelial cell marker lectin and anti-AQP4 antibody. We also performed Western blot to examine the effects of ECS on the hippocampal expression of AQP4 and the tight junction molecule claudin-5., Results: Gunn rats showed learned helplessness and impaired spatial working memory, compared to normal control Wistar rats. ECS significantly improved the depressive-like behavior. Gunn rats showed a decrease in astrocytic coverage of blood vessels, that was significantly increased by ECS. ECS significantly increased expression of AQP4 and claudin-5 in Gunn rats., Conclusions: ECS increased the reduced coverage of blood vessels by astrocytic endfeet in the mPFC and hippocampus with amelioration of depressive-like behavior. Therefore, therapeutic mechanism of ECT may involve restoration of the impaired gliovascular units by increasing the astrocytic-endfoot coverage of blood vessels., (Copyright © 2019. Published by Elsevier B.V.)

A reduction of GABAergic markers in postmortem tissue is consistently found in schizophrenia. Importantly, these alterations in GABAergic neurons are not global, which means they are more prevalent among distinct subclasses of interneurons, including those that express the calcium binding protein parvalbumin. A decreased expression of parvalbumin in the hippocampus is a consistent observation not only in postmortem human schizophrenia patients, but also in a diverse number of rodent models of the disease. Meanwhile, previously we reported that the congenital hyperbilirubinemia model rats (Gunn rats), which is a mutant of the Wistar strain, showed behavioral abnormalities, for instance, hyperlocomotor activity, deficits of prepulse inhibition, inappropriate social interaction, impaired recognition memory similar with several rodent models of schizophrenia. Several animal studies linked the importance of palvalbumin in relation to abnormal hippocampal activity and schizophrenia-like behavior. Here, we show that parvalbumin positive cell density was significantly lower in the CA1, CA3 and the total hippocampus of Gunn rats (congenital hyperbilirubinemia model rats) compared to Wistar control rats. The correlations between serum UCB levels and loss of PV expression in the hippocampus were also detected. The decreases in the PV-expression in the hippocampus might suggest an association of the behavioral abnormalities as schizophrenia-like behaviors of Gunn rats, compared to the Wistar control rats.

Background: There is evidence that several intervention types, including psychotherapy, reduce repeat suicide attempts. However, these interventions are less applicable to the heterogeneous patients admitted to emergency departments (EDs). The risk of a repeat suicide attempt is especially high in the first 6 months after the initial attempt. Therefore, it is particularly important to develop effective ED interventions to prevent repeat suicide attempts during this 6-month period., Methods: We systematically reviewed randomized controlled trials of ED-initiated interventions for suicidal patients admitted to EDs using the databases MEDLINE, PsychoINFO, CINAHL, and EMBASE up to January 2015 in accordance with an a priori published protocol (PROSPERO: CRD42013005463). Interventions were categorized into four types, including active contact and follow-up interventions (intensive care plus outreach, brief interventions and contact, letter/postcard, telephone, and composite of letter/postcard and telephone), and a meta-analysis was conducted to determine pooled relative risks (RRs) and 95% confidence intervals (CIs) of a repeat suicide attempt within 6 months., Results: Of the 28 selected trials, 14 were active contact and follow-up interventions. Two of these trials (n = 984) reported results at 6 months (pooled RR = 0.48; 95% CI: 0.31 to 0.76). There were not enough trials of other interventions to perform meta-analysis. Some trials included in the meta-analysis were judged as showing risk of bias., Conclusion: Active contact and follow-up interventions are recommended for suicidal patients admitted to an ED to prevent repeat suicide attempts during the highest-risk period of 6 months., Systematic Review Registration: PROSPERO CRD42013005463 (27 August 2013).

Background: Smoking behavior among people with serious psychological distress (SPD) has not been fully investigated in Asia, although smoking has become a public health concern worldwide. Many Western population-based studies indicate that people with psychological distress are more likely to smoke., Methods: This study used a national representative data set from the 2010 Comprehensive Survey of Living Conditions of Japan. SPD was defined as scores ≥13 or greater on the Kessler Psychological Distress Scale (K6). Multivariate logistic regression analyses were conducted to analyze the association between SPD and current smoking in Japanese adults., Results: In both men (n = 27,937) and women (n = 30,786), SPD was significantly associated with current smoking (adjusted odds ratios [95% confidence intervals]: 1.169 [1.030-1.328] for men and 1.677 [1.457-1.931] for women). Among men, SPD was significantly associated with current smoking only in people aged ≥50 years (1.519 [1.232-1.874]) and married (1.456 [1.228-1.728]). SPD was significantly associated with current smoking in women of all ages. SPD had a greater impact on current smoking for women aged 20-49 years than for those aged ≥50 years (1.832 [1.552-2.162] and 1.445 [1.099-1.900], respectively)., Limitations: The cross-sectional design precludes assumptions about the direction of causality. In addition, smoking status was self-reported., Conclusions: SPD was significantly associated with current smoking in Japan and the association was much stronger for younger women. Clinical strategies are needed to reduce the prevalence of smoking among people with SPD to reduce excess mortality in this population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished., Methods: This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates., Results: Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects., Conclusions: In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine., Trial Registration: ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.

Background: It is unclear whether individuals who have serious psychological distress (SPD) are less likely to participate in screening tests for gastric cancer, lung cancer, and other types of cancer. Of the few studies that have examined the association between SPD and participation in cancer screening, none have reported modifying effects of educational, marital, or employment status., Methods: The authors analyzed a national representative data set from the 2010 Comprehensive Survey of Living Conditions of Japan., including individuals aged <69 years who met the national program criteria for each type of cancer screening (colorectal, gastric, and lung cancers, n = 29,926; breast cancer, n = 15,423; and cervical cancer, n = 24,735). SPD was defined as a score of 13 or greater on the Kessler 6 scale. Logistic regression analyses were conducted to examine the association between SPD and participation in cancer screening, and multivariate analyses stratified by socioeconomic status also were conducted., Results: SPD was significantly associated with a lower odds ratio (OR) for participation in screening for colorectal cancer (OR, 0.743; 95% confidence interval [CI], 0.638-0.866), gastric cancer (OR, 0.823; 95% CI, 0.717-0.946), and lung cancer (OR, 0.691; 95% CI, 0.592-0.807). Only educational status significantly modified the effect of SPD on participation in these 3 types of cancer screening (P < .05)., Conclusions: Individuals with SPD, especially those with lower education levels, were less likely to participate in screening for colorectal, gastric, and lung cancers. Individuals with SPD should be encouraged and supported to participate in cancer screening tests. Cancer 2018;124:555-62. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Aim: The influence of schizophrenic patients' functional disability on cancer screening participation worldwide is unclear. There are few findings on the disparities in schizophrenic patients' participation in cancer screening programs in Asia. The aim of this study was to investigate the screening rate and the associations between screening and symptom severity/functional disability in patients with schizophrenia., Methods: This cross-sectional study was conducted in a psychiatric hospital outpatient clinic in Japan. We recruited schizophrenic patients meeting the national program criteria for cancer screening for colorectal, gastric, lung, breast, and cervical cancer (n = 224, 223, 224, 110, and 175, respectively). Receipt of cancer screenings was assessed using a self-report questionnaire. Scores on the modified Global Assessment of Functioning (mGAF) were evaluated by participants' primary psychiatrists., Results: Rates of cancer screenings were as follows: 24.1% for colorectal, 21.5% for gastric, 30.8% for lung, 25.5% for breast, and 19.4% for cervical cancer. A multivariable logistic analysis showed that a 1-point increase in severity/disability (100 minus mGAF score) was associated with significantly lower odds ratios (OR) for receipt of cancer screenings, except for breast cancer (OR, 0.95, 95% confidence interval [CI], 0.93-0.98 for colorectal; OR, 0.96, 95%CI, 0.93-0.98 for gastric; OR, 0.95, 95%CI, 0.93-0.97 for lung; OR, 0.97, 95%CI, 0.94-1.00 for breast; and OR, 0.95, 95%CI, 0.92-0.98 for cervical cancer)., Conclusion: The findings demonstrated low rates of cancer screenings in schizophrenic patients in Japan. Our study suggests the need to encourage attendance at cancer screenings, especially in schizophrenic patients with severe symptoms/functional disability., (© 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.)

Objective. To measure whether Emotional intelligence (EI) would minimize the negative association between autistic-like traits (ALT) and empathic behavior and enhance the positive association between ALT and psychological distress. Methods. Our sample population included 823 hospital pharmacists belonging to a district society, and 378 pharmacy students. Analyses were performed to examine relationships between scores on the Emotional Intelligence Scale (EQS), Autism-Spectrum Quotient (AQ), Jefferson Scale of Empathy (JSE), and General Health Questionnaire-12 (GHQ). Results. Complete answers were obtained from 373 pharmacists, and 341 students. EQS partially intervened the associations between AQ and JSE and between AQ and GHQ. Conclusion. EI partially intervened the relationships between ALT and empathy, and between ALT and mental health, both of which are necessary for optimal pharmaceutical practice.

Many patients with schizophrenia have poor clinical and social outcomes. Some risk alleles closely related to the onset of schizophrenia have been reported to be associated with their clinical phenotypes, but the direct relationship between genetic vulnerability to schizophrenia and clinical/social outcomes of schizophrenia, as evaluated by both practical clinical scales and 'real-world' function, has not been investigated. We evaluated the clinical and social outcomes of 455 Japanese patients with schizophrenia by severity of illness according to the Clinical Global Impression-Severity Scale (CGI-S) and social outcomes by social adjustment/maladjustment at 5 years after the first visit. We examined whether 46 single nucleotide polymorphisms (SNPs) selected from a Japanese genome-wide association study of susceptibility to schizophrenia were associated with clinical and social outcomes. We also investigated the polygenic risk scores of 46 SNPs. Allele-wise association analysis detected three SNPs, including rs2623659 in the CUB and Sushi multiple domains-1 (CSMD1) gene, associated with severity of illness at end point. The severity of illness at end point was associated with treatment response, but not with the severity of illness at baseline. Three SNPs, including rs2294424 in the C6orf105 gene, were associated with social outcomes. Point estimates of odds ratios showed positive relationships between polygenic risk scores and clinical/social outcomes; however, the results were not statistically significant. Because these results are exploratory, we need to replicate them with a larger sample in a future study.

Background: Pharmacists are expected to play a key role in modern cancer care. Research suggests that an empathic approach and attitude in medical staff improves the quality of patient care. An empathic attitude and psychological distress are thought to be associated with autistic-like traits, but little is known about such traits., Objective: In this study, we aimed to clarify the associations among autistic-like traits, empathic attitude in a medical context, and psychological health in hospital pharmacists., Setting: Eligibility criteria for inclusion were certified pharmacists working at hospitals for patient care who returned their questionnaires., Method: Eight hundred and twenty-three hospital pharmacists completed a number of self-administered questionnaires anonymously by mail., Main Outcome Measures: Scores were obtained on the Autism-Spectrum Quotient, the Jefferson Scale of Empathy, the General Health Questionnaire-12, and subscales of the Interpersonal Reactivity Index (Perspective Taking, IRI-Empathic Concern, IRIPersonal Distress). We performed correlation and mediation analyses to confirm that the empathy and general health questionnaires were associated with autism-spectrum quotient scores, and with each IRI subscale., Results: Complete responses were obtained from 379 pharmacists comprising 151 males (39.8 %) with a mean age of 37.7 ± 10.8 years (missing data, n = 13) and a median of 11 years after qualification as a pharmacist. Autism-Spectrum Quotient scores were inversely correlated with empathy (r = -0.22, p < 0.001) and positively correlated with general health scores (r = 0.40, p < 0.001). In the models with mediation, the inverse correlation between autism-spectrum quotient and empathy scores was mediated indirectly by IRI-Perspective Taking and IRI-Empathic Concern, and the positive correlation between autism-spectrum quotient and general health was mediated indirectly by IRI-Personal Distress. There were also direct effects, with significant effects of autism-spectrum quotient on empathy and general health scores., Conclusion: Our findings suggest that autistic-like traits affect both empathic attitude in a medical context and the psychological health of pharmacists. We recommend that to improve empathy in those with high levels of autistic-like traits, we may need to develop specialized interventions, such as improving communication skills training.

Background: SUN(^&#95;^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multicenter pragmatic mega-trial to examine the optimum treatment strategy for the first- and second-line treatments for unipolar major depressive episodes. The trial has three steps and two randomizations. Step I randomization compares the minimum and the maximum dosing strategy for the first-line antidepressant. Step II randomization compares the continuation, augmentation or switching strategy for the second-line antidepressant treatment. Step III is a naturalistic continuation phase. The original protocol was published in 2011, and we hereby report its updated protocol including the statistical analysis plan., Results: We implemented two important changes to the original protocol. One is about the required sample size, reflecting the smaller number of dropouts than had been expected. Another is in the organization of the primary and secondary outcomes in order to make the report of the main trial results as pertinent and interpretable as possible for clinical practices. Due to the complexity of the trial, we plan to report the main results in two separate reports, and this updated protocol and the statistical analysis plan have laid out respective primary and secondary outcomes and their analyses. We will convene the blind interpretation committee before the randomization code is broken., Conclusion: This paper presents the updated protocol and the detailed statistical analysis plan for the SUN(^&#95;^)D trial in order to avoid reporting bias and data-driven results., Trial Registration: ClinicalTrials.gov: NCT01109693 (registered on 21 April 2010).

Background: Major depression is one of the most debilitating diseases in terms of quality of life. Less than half of patients suffering from depression can achieve remission after adequate antidepressant treatment. Another promising treatment option is cognitive-behavior therapy (CBT). However, the need for experienced therapists and substantive dedicated time prevent CBT from being widely disseminated. In the present study, we aim to examine the effectiveness of switching antidepressants and starting a smartphone-based CBT program at the same time, in comparison to switching antidepressants only, among patients still suffering from depression after adequate antidepressant treatment., Methods/design: A multi-center randomized trial is currently being conducted since September 2014. The smartphone-based CBT program, named the "Kokoro-App," for major depression has been developed and its feasibility has been confirmed in a previous open study. The program consists of an introduction, 6 sessions and an epilogue, and is expected to be completed within 9 weeks by patients. In the present trial, 164 patients with DSM-5 major depressive disorder and still suffering from depressive symptoms after adequate antidepressant treatment for more than 4 weeks will be allocated to the Kokoro-App plus switching antidepressant group or the switching antidepressant alone group. The participants allocated to the latter group will receive full components of the Kokoro-App after 9 weeks. The primary outcome is the change in the total score on the Patient Health Questionnaire through the 9 weeks of the program, as assessed at week 0, 1, 5 and 9 via telephone by blinded raters. The secondary outcomes include the change in the total score of the Beck Depression Inventory-II, change in side effects as assessed by the Frequency, Intensity and Burden of Side Effects Rating, and treatment satisfaction., Discussion: An effective and reachable intervention may not only lead to healthier mental status among depressed patients, but also to reduced social burden from this illness. This paper outlines the background and methods of a trial that evaluates the possible additive value of a smartphone-based CBT program for treatment-resistant depression., Trial Registration: UMIN-CTR: UMIN000013693 (registered on 1 June 2014).

Background: A huge number of patients with self-harm and suicide attempt visit emergency departments (EDs). We systematically reviewed studies and examined the effect of interventions to prevent repeat suicidal behavior in patients admitted to EDs for a suicidal attempt., Method: We searched the databases of MEDLINE, PsychoINFO, CINAHL, and EMBASE through August 2013. Eligible studies were randomized controlled trials assessing the effects on repeat suicidal behavior of interventions initiated in suicidal patients admitted to EDs. Interventions in each trial were classified into groups by consensus. Meta-analyses were performed to determine pooled relative risks (RRs) and 95% confidence intervals (CIs) of repetition of suicide attempt for interventions in each group., Results: Out of 5390 retrieved articles, 24 trials were included and classified into four groups (11 trials in the Active contact and follow-up, nine in the Psychotherapy, one in the Pharmacotherapy, and three in the Miscellaneous). Active contact and follow-up type interventions were effective in preventing a repeat suicide within 12 months (n=5319; pooled RR=0.83; 95% CI: 0.71 to 0.97). However, the effect at 24 months was not confirmed (n=925; pooled RR=0.98; 95% CI: 0.76-1.22). The effects of the other interventions on preventing a repetition of suicidal behavior remain unclear., Limitation: Caution is needed regarding the heterogeneity of the effects., Conclusion: Interventions of active contact and follow-up are recommended to reduce the risk of a repeat suicide attempt at 12 months in patients admitted to EDs with a suicide attempt. However, the long-term effect was not confirmed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: There have been very few population-based prospective studies that have investigated the risks of deaths by suicide and other externally caused injuries (ECIs) among cancer patients in an Asian population. This study investigated whether the risk of death by both suicide and ECIs increases during the first year following the initial diagnosis of cancer., Methods: Data were analyzed from a population-based cohort of Japanese residents between 1990 and 2010, collected during the Japan Public Health Center-based Prospective Study. Poisson regression models were used to calculate adjusted risk ratios (RRs) for both suicide and ECI deaths. To adjust for unmeasured confounding factors, case-crossover analyses were conducted for all patients with cancer who died by suicide and ECIs., Results: A population-based cohort of 102,843 Japanese residents was established. During the follow-up period, there were 34 suicides and 48 ECI deaths among patients with cancer, as compared with 527 suicides and 707 ECI deaths among those who did not have cancer. Analyses revealed that those who were newly diagnosed with cancer were at a greatly increased risk of death by suicide and ECIs within the first year after their diagnosis (suicide RR = 23.9, 95% CI: 13.8-41.6; ECI RR = 18.8, 95% CI: 11.4-31.0). Furthermore, the case-crossover analyses generally confirmed the results of the Poisson regressions., Conclusions: The risks of suicide and ECI deaths within the first year after a cancer diagnosis were higher than those among cancer-free populations. A diagnosis of cancer is a critical experience that may increase the risk of fatal outcomes., (Copyright © 2014 John Wiley & Sons, Ltd.)

In view of the fact that the suicide rate in Japan has remained high since 1998, the Basic Act on Suicide Prevention was implemented in 2006 with the objective of comprehensively promoting suicide prevention measures on a national scale. Based on this Basic Act, in 2007, the Japanese government formulated the General Principles of Suicide Prevention Policy as a guideline for recommended suicide prevention measures. These General Principles were revised in 2012 in accordance with the initial plan of holding a review after five years. The Basic Act places an emphasis on the various social factors that underlie suicides and takes the perspective that suicide prevention measures are also social measures. The slogan of the revised General Principles is "Toward Realization of a Society in which Nobody is Driven to Commit Suicide". The General Principles list various measures that are able to be used universally. These contents would be sufficient if the objective of the General Principles were "realization of a society that is easy to live in"; however, the absence of information on the effectiveness and order of priority for each measure may limit the specific effectiveness of the measures in relation to the actual prevention of suicide. In addition, considering that nearly 90% of suicide victims are in a state at the time of committing suicide in which a psychiatric disorder would be diagnosed, it would appear from a psychiatric standpoint that measures related to mental health, including expansion of psychiatric services, should be the top priority in suicide prevention measures. However, this is not the case in the General Principles, in either its original or revised form. Revisions to the General Principles related to clinical psychiatry provide more detailed descriptions of measures for individuals who unsuccessfully attempt suicide and identify newly targeted mental disorders other than depression; however, the overall proportion of contents relating to psychiatric care remains small. In particular, it must be noted that almost no measures are provided for individuals with chronic psychiatric disorders. We believe that the role of academic societies involved in suicide prevention, including our own, is to organize the contents of the General Principles based on evidence, to advance research in areas lacking in evidence, and to promote support for implementation of activities in areas with clear evidence.

Objective: Two depression screening tools, Patient Health Questionnaire (PHQ)-9 and PHQ-2, have not had their validity examined in general internal medicine settings in Japan. We examined the validity of these screening tools., Methods: A total of 598 outpatients of an internal medicine clinic in a rural general hospital were enrolled consecutively and stratified by PHQ-9 score. Seventy-five patients randomly selected and 29 patients whose results from the PHQ-9 were considered to be positive for depressive disorder were then interviewed with a semistructured interview, the Mini International Neuropsychiatric Interview. We calculated diagnostic accuracy of the PHQ-9 and PHQ-2 to detect major depression and that of the suicidality item of the PHQ-9 to detect suicidality using sampling weights with multiple imputations., Results: Sensitivity and specificity for depression were 0.86 and 0.85, respectively, for the PHQ-9 with cutoff points of 4/5, and 0.77 and 0.95, respectively, for the PHQ-2 with cutoff points of 2/3. Sensitivity and specificity of the suicidality item of the PHQ-9 were 0.70 and 0.97, respectively., Conclusion: In internal medicine clinics in Japanese rural hospitals, the PHQ-2 with an optimal cutoff point for each setting plus the suicidality item of the PHQ-9 can be recommended to detect depression without missing suicidality., (© 2013.)

Purpose: Previous studies have reported associations of depressive symptoms with pro-inflammatory cytokines, especially with interleukin-6 (IL-6) in noncancer subjects and cancer patients. Meanwhile, symptoms such as tiredness and appetite loss may be vegetative symptoms of depression when associated with other diagnostic criteria of depression. Such vegetative-type symptoms worsen during the last 6 months of life in cancer patients and may not be associated with affective depressive symptoms such as sadness and nervousness. This study explored associations between depressive symptoms and plasma IL-6 in terminally ill cancer patients whose survival period was confirmed to be less than 6 months by follow-up, with attention to differences in vegetative and affective depressive symptoms., Methods: Data from 112 consecutively recruited terminally ill cancer patients who registered at a palliative care unit without any active anticancer treatment were used. Plasma IL-6 levels were measured using an electrochemiluminescence assay. Depressive symptoms included in the DSM-IV and Cavanaugh criteria were assessed by structured interviews and were categorized into affective symptoms and vegetative symptoms. Affective symptoms were also measured with the depression subscale of the Hospital Anxiety and Depression Scale, which does not include vegetative symptoms., Results: Vegetative symptoms, such as appetite loss, insomnia, and fatigue, were significantly associated with IL-6 levels. However, neither of the affective symptoms nor their severity was associated with IL-6 levels., Conclusions: IL-6 was associated with vegetative depressive symptoms in terminally ill cancer patients but not with affective depressive symptoms, suggesting possible differences in the pathophysiological mechanisms between these sets of symptoms.

Objective: In Europe and the US, primary care has been anticipated in identifying untreated depression. Findings show a high prevalence of depression in such settings. However, the prevalence of depression in an internal medicine clinic in a rural area of Japan, which has a role in primary care, is unclear., Method: The prevalence of depression and comorbid psychiatric disorders among outpatients of an internal medicine clinic in a rural general hospital was measured by a structured interview using the Mini International Neuropsychiatric Interview. Outpatients were recruited consecutively and stratified by Patient Health Questionnaire-9 (PHQ-9) scores. Among 598 outpatients, we interviewed 75 randomly selected patients and 29 whose results of the PHQ-9 were positive. We estimated prevalence of depressive episode using age, sex, physical findings by internal medical doctors and PHQ-9 scores as covariates., Results: The estimated prevalence of major and minor depressive episodes were 7.4% [95% confidence interval (CI): 3.4%-11.4%] and 6.8% (95% CI: 2.6%-10.9%), respectively. Among major depressed patients, 71.4% had current suicidal ideation., Conclusion: Given the high rate of depression and suicidality, identification of depression and collaboration between internal medical doctors in a rural area of Japan and mental health professionals are needed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We have previously demonstrated that riluzole has anxiolytic-like effects in rats, without affecting spontaneous alternation performance in the Y-maze test. However, the effects of riluzole on hippocampal synaptic plasticity were still unclear. In this study, we showed that bath application of riluzole did not impair long-term potentiation and long-term depression, whereas a benzodiazepine anxiolytic, diazepam, significantly impaired them. Furthermore, the acquisition of spatial memory in the Morris water maze test was impaired in diazepam-treated but not riluzole-treated rats. We thus provide further evidence for the potential usefulness of riluzole as an anxiolytic that does not cause amnesia.

Pancreatic cancer is characterized by a high frequency of cachexia, pain and neural invasion (N-inv). Neural damage is occurred by N-inv and modulates pain and muscle atrophy via the activation of astrocyte in the connected spine. The activated astrocyte by N-inv, thus, may affect cachexia in pancreatic cancer. Clinical studies in patients and autopsy cases with pancreatic cancer have revealed that N-inv is related to cachexia and astrocytic activation. We established a novel murine model of cancer cachexia using N-inv of human pancreatic cancer cells. Mice with N-inv showed a loss of body weight, skeletal muscle and fat mass without appetite loss, which are compatible with an animal model of cancer cachexia. Activation of astrocytes in the spinal cord connected with N-inv was observed in our model. Experimental cachexia was suppressed by disrupting neural routes or inhibiting the activation of astrocytes. These data provide the first evidence that N-inv induces cachexia via astrocytic activation of neural route in pancreatic cancer., (Copyright © 2012 UICC.)

Suicide rate in Japan is 25/100,000 in a year. The rate is higher than those in other developed countries. Physical illness is a risk factor for suicide. To prevent suicide in patients with physical illness, identification of mental illness, such as depression, is important. In addition, palliative care for distressing physical and psychological symptoms is also important. In process of identification of mental illness and distressing physical symptoms, communications between medical staff and patients are essential. Enhancing communication skills of medical staff may be a key point to prevent suicide.

Since the promulgation of the Basic Act for Suicide Prevention, suicide prevention in Japan has developed rapidly. In order to further reinforce such activities, it is necessary to balance universal, selective, and indicated prevention. For the revision of the General Principles of Suicide Prevention Policy, the Center for Suicide Prevention announced this recommendation with 29 societies. We hope that it will promote suicide prevention in Japan and lead to expansion of the suicide prevention network by academic organizations, NGOs, as well as local and central government.

Previous studies have reported the existence of an association between brain-derived neurotrophic factor and major depression. However, the possible role of brain-derived neurotrophic factor in the pathophysiology of major depression after cancer diagnosis has not yet been investigated. Subjects were collected using the Lung Cancer Database project. Using the cut-off scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), 81 subjects with depression (HADS-D > 10) and 81 subjects without depression (HADS-D < 5) were selected. The two groups were matched for age, sex, clinical stage and performance status. The serum brain-derived neurotrophic factor levels were measured using an enzyme-linked immunosorbent assay method. The serum brain-derived neurotrophic factor levels were not statistically different between the subjects in the depression group [29.1 (13.6) ng/ml; mean (SD)] and the non-depression group [31.4 (10.6) ng/ml] (P = 0.22). In a stratified analysis by gender, however, the mean serum brain-derived neurotrophic factor level in the depression group tended to be lower than that in the non-depression group among women (n = 24 pairs, P = 0.06). Major depression after cancer diagnosis is not associated with serum brain-derived neurotrophic factor levels.

Effective intervention models for depressed patients in primary care settings have been developed in other countries. In Japan, a general internist has an important role in primary care. However, there is little information on the prevalence of depression and the rate of its recognition by general internists in Japan. The present study surveyed these data in a general internal medicine outpatient clinic in a Japanese rural hospital. Results showed the prevalence of depression to be relatively high. Most depressed patients were recognized by physicians as having a mental disorder, but only a few were diagnosed as having a mood disorder. Despite a high prevalence of depression, physicians did not recognize it. Development of an optimized model to screen and introduce appropriate care for depressed patients is needed.

Fatigue is one of the most distressing symptoms among terminally ill cancer patients. However, no effective intervention has been established. Several studies have suggested the role of cytokines in fatigue in cancer patients receiving anti-cancer treatment, patients with metastatic cancer, and cancer survivors, but not in terminally ill cancer patients. In the present study, the potential association between fatigue and plasma interleukin-6 (IL-6) was examined in 46 terminally ill cancer patients (median survival: 64.5 days) who received neither steroids nor nonsteroidal anti-inflammatory drugs. Fatigue was evaluated by the Cancer Fatigue Scale (CFS), which consists of multiple dimensions of fatigue, such as Physical, Affective, and Cognitive subscales. Plasma IL-6 levels were measured using an enzyme-linked immunosorbent assay and were compared between patients with and without "clinical fatigue" as defined by the total score of the CFS. Additionally, associations between each of the CFS scores and IL-6 levels were examined. As a result, the IL-6 level in patients with clinical fatigue (n=27 [59%]; mean, SD, median, and range: 37.1, 46.4, 17.1, and 3.7-182.5pg/ml, respectively) was significantly higher than those without clinical fatigue (n=19 [41%]; mean, SD, median, range: 14.3, 12.2, 8.0, and 2.8-45.0pg/ml, respectively) (P=0.02). The IL-6 level significantly correlated with the Physical subscale score (r=0.35, P=0.02), but not with other subscale scores. In conclusion, IL-6 may play a role in fatigue, especially in the physical dimension, in terminally ill cancer patients. The results of the present study provide information to develop a new treatment strategy for cancer fatigue in terminally ill cancer patients.

Both the hippocampus and amygdala are frequently targeted by researchers and clinicians for volumetric analysis based on magnetic resonance imaging (MRI). However, different data acquisition, analysis software and anatomical boundaries have in the past made it difficult to compare results of MRI studies from different laboratories. A reliable original segmentation protocol for volumetry of the amygdala and hippocampus on three-dimensional MRI was established by including merits of previous volumetric studies. Two skilled raters measured randomly selected 20 subjects from 242 subjects recently scanned in our institution (mean age 47.6 +/- 6.1 years). Data acquisition was performed with a three-dimensional spoiled gradient echo technique. Volumetric analysis was performed manually using three-dimensional software that allowed coronal, sagittal, and transverse images at any time. Both intra- and inter-rater reliability (intraclass correlation coefficients) yielded 0.99 for the hippocampus and 0.98 for the amygdala. It was confirmed that this segmentation protocol was highly reliable.